Complex biologically active molecules are challenging, expensive, and time-consuming to synthesize. Synthesizing chiral, non-racemic compounds with good enantio- and diastereoselectivity is even more challenging. An example of such a molecule is Compound 1:
This compound is a potent inhibitor of the hepatitis C virus (HCV) NS3/4A protease; it shows broad genotype activity and substantially improved in vitro profile compared to earlier generation HCV NS3/4A protease inhibitors.
The original synthesis of this compound requires a ring closing metathesis (RCM) reaction for synthesis of the macrocycle (see WO 2012/040167). However, this RCM reaction involves high catalyst loading and expensive starting materials, resulting in low throughput due to dilute reaction conditions and increased costs.
There exists a need for new, efficient synthetic methods to construct Compound 1.